Single Institutional Experience with Metachromatic Leukodystrophy: Demographic, Biochemical and Genetic Characteristics of 7 Patients

Introduction: Metachromatic leukodystrophy (MLD) is a demyelination, autosomal recessive lysosomal storage disease caused by biallelic pathogenic mutations in the ARSA and PSAP genes that results in deficient arylsulfatase A enzyme activity. It causes pathologic sulfatide accumulation in myelin sheaths in the central and peripheral nervous system, with developmental and neurocognitive progressive deterioration observed in all age groups. Although there is no curative treatment for all types and stages, hematopoietic stem cell transplantation (HSCT) and umbilical cord blood transplantation (UCBT) are the most promising treatment modalities in asymptomatic or early symptomatic juvenile-onset disease.

Materials and Method: Seven patients from five different families were diagnosed genetically and enzymatically with MLD.

Results: Two patients were diagnosed by family screening in the asymptomatic period. Parental consanguinity was present in all patients and all patients had the late infantile form. The mean age of the patients was 28 months (range 3−36 months) and the mean onset of diagnosis was 21.6 months (range 3−30 months). Neuromotor developmental delay was present in five patients. HSCT was performed on the 3-month-old asymptomatic sibling and well tolerated. Neurological symptoms did not occur in the 12-month clinical follow-up period and the control ARSA enzyme level was in the normal range. HSCT was also planned for the other sibling whose clinical status was asymptomatic with abnormal cranial MRI findings.

Discussion: Herein, we present the clinical, biochemical and genetic characteristics of 7 MLD patients. It is important to diagnose in the asymptomatic period and HSCT could be a viable treatment option. Late infantile phenotypes may benefit from early, pre-symptomatic transplant. Newborn and family screening for MLD patients could be important for early diagnosis.